Danilo Rocco, Luigi Della Gravara, Giovanni Palazzolo, Cesare Gridelli
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引用次数: 0
摘要
截至目前,仅有两种抗血管生成单克隆抗体加表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKI)的组合获得了美国食品药品管理局(FDA)和欧洲药品管理局(EMA)的批准,并被美国临床肿瘤学会、欧洲肿瘤内科学会和美国国家综合癌症网络推荐用于EGFR+晚期非小细胞肺癌患者的一线治疗:厄洛替尼加贝伐单抗和厄洛替尼加雷莫芦单抗。然而,由于几种不同的获得性耐药机制,主要是以T790M置换和MET扩增为代表的耐药机制,所有接受治疗的患者最终都会对这类药物失去反应。尽管奥希替尼治疗 T790M+ 患者仍是唯一获批的治疗方法,但在不久的将来,MET-TKIs 很可能会改变这一现状。事实上,现有的临床数据有力地支持了以 MET-TKI 为基础的联合疗法在表皮生长因子受体(EGFR)+ MET 扩增患者中的作用,可能会彻底改变我们目前的治疗算法。化疗加免疫治疗加抗血管生成治疗的联合疗法也可能是另一种有益的补充。
The role of antiangiogenic monoclonal antibodies combined to EGFR-TKIs in the treatment of advanced non-small cell lung cancer with activating EGFR mutations: acquired resistance mechanisms and strategies to overcome them.
As of today, only two antiangiogenic monoclonal antibodies plus epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) combinations are FDA and EMA-approved and are recommended by American Society of Clinical Oncology, European Society for Medical Oncology, and National Comprehensive Cancer Network for the first-line treatment of EGFR+ advanced non-small cell lung cancer patients: erlotinib plus bevacizumab and erlotinib plus ramucirumab. However, all treated patients eventually become unresponsive to such drugs, due to several different acquired resistance mechanisms, mainly represented by T790M substitutions and MET amplifications. While osimertinib treatment in T790M+ patients still represents the only approved treatment, MET-TKIs will likely change this status quo in the near future. In fact, existing clinical data strongly support a role for MET-TKI-based combinations in EGFR+ MET-amplified patients, possibly revolutionizing our current treatment algorithm. Chemotherapy plus immunotherapy plus antiangiogenic therapy combinations could also represent another useful addition.